Tetra Discovery Partners proposes to develop a new treatment for major depressive disorder based on inhibition of phosphodiesterase 4B (PDE4B). Uniquely, the Tetra drug will address inflammation as a contributor to depression. This is a new mechanism of action for an antidepressant drug which should prove complimentary to current therapeutics. Addressing inflammation will target currently untreatable patients, such as those receiving interferon-a (IFNa) for viral illness, depressed patients with co-morbid psoriasis, inflammatory bowel disease, traumatic brain injury, or post-traumatic stress disorder. Given the limitations of current treatments, there is a need for new medications with novel mechanisms of action. The prevalence of major depression is staggering with around 20% of people experiencing depression at some point in their lives. The company estimates that 10-20% of patients with depression have inflammation and will be ideal candidates for the Tetra drug. The market for antidepressant drugs is expected to grow at a CAGR of 3.2% to US $10.9 billion by 2018. The World Health Organization predicts that by 2020, depression will rival heart disease as the health disorder with the highest disease burden in the world. The Phase II SBIR project will complete chemical optimization of a PDE4B inhibitor for use in human and the preclinical safety and toxicity studies needed for filing an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) for human clinical trials in major depression.